Abstract: The present invention has designed and produced a family of recombinant proteins that could provide broad-spectrum protection/neutralization against most subtypes of TcdB, and therefore could be developed into therapies against GDI. The designs of these novel proteins are based on the first 3D structure of TcdB1 in complex with its receptor CSPG4 that was recently determined. The present invention demonstrates that these newly designed proteins are more potent and provide broader-spectrum protection than the commercial antibody bezlotoxumab in terms of neutralizing diverse subtypes of TcdB.

Abstract: Methods and compositions for treating or preventing C. difficile infection (CDI) through TcdB or TcdA holotoxins. The compositions feature immunogens or binding agents, such as antibodies, nanobodies (VHHs), single-domain antibodies (sdAbs), etc., based on one or a combination of neutralizing epitopes of TcdB or TcdA. Where immunogens inhibit the conformational changes necessary for pore formation by TcdB at an endosomal pH. Additionally, immunogens inhibit the movement of the scissile bond into the CPD cleavage side and a proper orientation of GTD relative to CPD, thus inhibiting cleavage of the GTD, which is required to activate the toxin. The present invention also describes vaccines for treatment of CDI, e.g., vaccines that target TcdB or TcdA.

Abstract: Provided herein are agents that bind to the lipid binding groove of Frizzled (FZD). In some embodiments, the agent is a fragment of TcdB corresponding to amino acids 1285-1804 of SEQ ID NO: 1. In some embodiments, binding of the agent to the lipid binding groove of FZD inhibits TcdB entry into cells, and/or inhibits Wnt signaling. Methods of treating Clostridium difficile infection (CDI) and methods of treating cancer are also provided.